INTRODUCTION
Postoperative nausea and vomiting (PONV) continues to be common complication of anesthesia and surgery in spite of availability of so many antiemetic drugs and regimens for prevention. The overall incidence of PONV is reported to be between 20% and 30%, but it can increase up to 80% in high-risk patients.[1 2 3
PONV is thought to be multifactorial involving anesthetic, surgical, and individual risk factors. PONV incidence is more than 50% in laparoscopic hernia repair, laparoscopic cholecystectomy, laparoscopic gynecologic surgery performed under general anesthesia.[4 5
LEVOSULPIRIDE is a levo-enantiomer of sulpiride, a central and peripheral dopaminergic D2 receptor antagonist. In the central nervous system, it specifically antagonizes D2 receptors in Area Prostrema of the 4th ventricle and in the gastrointestinal system antagonizes D2 receptors in submucosal and myenteric plexus. Plasma half-life is 6-8 h and primarily excreted through the renal route.[6 7 8 9
RAMOSETRON is a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist. Central 5-HT3 receptors are present in solitary tract nucleus and chemoreceptor trigger zone, the peripheral 5-HT3 receptors are in vagal terminals linked to the vomiting center, Ramosetron blocks initiation of the vomiting reflex at these sites. Its plasma half-life is 5-6 h.[10 11 12
METHODOLOGY
Objectives
We conducted this study with the primary objective to compare the efficacy of intravenous (i.v.) Levosulpiride 25 mg with i.v. Ramosetron 0.3 mg in preventing PONV. We had secondary objective to compare the need for rescue medication and to study the adverse reactions with study drugs.
After obtaining Institutional Ethical Committee Clearance (SDMIEC/PG/0164/2018) and registered with CTRI (REF/2019/07/027428) and written informed consent from 200 patients of ASA Classes I and II aged between 18 and 60 years, undergoing laparoscopic surgeries of more than 1-h duration. We excluded emergency laparoscopic surgeries, smokers, significant liver disease or renal pathology, patients with H/o PONV and H/o allergy to Levosulpiride or Ramosetron . We also excluded pregnant and lactating mothers from the study.
Study period: November 2018 to June 2020.
Methods of collection of data
Study design
A prospective randomized double-blind control study.
Sample size
200.
Data collection
We followed the ethical principles for medical research involving human subjects according to the Helsinki Declaration October 2013. Two hundred patients undergoing laparoscopic surgery falling under the inclusion criteria were numbered and every nth patient is selected by systemic random sampling procedure and randomly allocated into two groups of 100 each, group Levosulpiride (Group L) and group Ramosetron (Group R) using the sealed envelope technique which was opened just before shifting patient to the operating room. The patient, person administering the study drug and doing postoperative assessment were different and blinded to study drug. Result values were recorded using a preset pro forma.
i.v. line was secured and study drug was given within 30 min of induction of anesthesia.
Group L: Received LEVOSULPIRIDE 25 mg i.v.
Group R: Received RAMOSETRON 0.3 mg i.v.
Preoperative assessment
Preoperative evaluation of all the patients was performed with detailed history, physical examination including height, weight, airway examination and systemic examination. Baseline investigations were done. The basal heart rate and blood pressure were recorded before surgery. All the patients kept nil per oral for solids for 8 h and were premedicated with Tablet Ranitidine 150 mg and Tablet alprazolam 0.25 mg on the night before the surgery. Verbal rating score for nausea was explained to the patient.
Induction and maintenance
In all patients, baseline vital parameters were noted. Anesthesia was induced with Fentanyl 2 μg.kg−1 and propofol 2 mg.kg−1 and trachealintubation facilitated with Vecuronium 0.1 mg.kg−1 . Anesthesia maintained with nitrous oxide in oxygen and a 11.5 minimum alveolar concentration of Isoflurane. At the completion of surgery, patients received neostigmine 0.05 mg.kg−1 and glycopyrrolate 0.008 mg.kg−1 for the reversal of neuro muscular blockade. Additional doses of Fentanyl used as per need.
Postoperative monitoring
The severity and extent of PONV were evaluated with regard to three specific entities, namely: (1) Incidence of nausea and vomiting, (2) rescue antiemetic used, and (3) nausea score.
An episode of vomiting is defined as either expulsion of stomach contents or an involuntary attempt to vomit without actual expulsion of stomach contents
Repeated vomiting occurring in a space of < 5 min is considered as a single episode
A combination of nausea and vomiting is considered as one entity under the category of vomiting
Nausea is scored with a verbal rating scale (from 0 = no nausea to 10 = worst nausea).
A rescue antiemetic (Dexamethasone 8 mg i.v.) given if the nausea was rated >5, if actual vomiting occurred, or at any time if requested by the patient. Nausea and vomiting assessment was made 30 min after the patient had been given rescue medication. If the PONV symptoms did not improve, another class of antiemeticthat is injected. Promethazine 12.5 mg i.v. which patient did not receive during the perioperative period was given for treatment.
A complete response was defined as the absence of PONV without antiemetic rescue during the 0-24 h postoperative period.
For postoperative pain, management Diclofenac 75 mg i.v. was given at the end of surgery at 12th and 24th h.
The occurrence of nausea and vomiting and rescue antiemetic drug use was monitored at 0-4 h, 4-8 h, 8-12 h, and 12-24 h.
Statistical analysis
All the data were collected, tabulated, and expressed as mean ± standard deviation.
Data were analyzed using IBM SPSS statistics for Windows. Version 22.0. Armonk, NY: IBM; 2013.
Unpaired sample t -test and Chi-square test has been used for the quantitative and qualitative data, respectively.
A P value of 0.05 was considered statistically insignificant.
RESULTS
A total of 200 patient population were randomized into two study groups as group L (n = 100) and group R (n = 100).
Table 1 shows the baseline demographic and clinical characteristics of the study population. Both the groups had almost similar demographic and clinical characteristics as there was no statistical difference between the two groups (P > 0.05).
Table 1: Comparison of sociodemographic and clinical characteristics between two groups
0-4 h: Twenty patients in levosulpiride group had any nausea or vomiting within first 4 h of the postoperative period, whereas 30 patients in ramosetron group experienced nausea and vomiting during this period and this finding was statistically not significant (P > 0.05).
4-8 h: Four patients in the levosulpiride group and five in ramosetron group experienced nausea and vomiting during this postoperative period and this difference was again not statistically significant (P > 0.05).
8-12 h: Five patients in the Levosulpiride group and four in the Ramosetron group experienced nausea and vomiting during this period and not statistically significant.
12-24 h: None of the patients had PONV during this period.
Use of rescue antiemetic at different duration between group L and group R is statistically insignificant (P > 0.05).
Table 2 shows the incidence of PONV and rescue anti-emetic of study population. The incidence of PONV and rescue anti-emetic at different duration between group L and group R is statistically insignificant (P > 0.05).
Table 2: Comparison of incidence postoperative nausea and vomiting and rescue anti-emetic among two groups
Table 3 shows the side effects in two study groups. Statistically incidence of headache is significant in Group R and incidence of sedation is significant in Group L.
Table 3: Comparison of side effects in two study groups
Table 4 shows Verbal Rating Scale score in both group R and L is statistically insignificant (P > 0.005) and signifies the incidence of nausea and vomiting is similar in both groups.
Table 4: Comparison of two groups (Levosulpiride and Ramosetron ) with Verbal Rating Scale scores at different duration by Mann-Whitney U -test
DISCUSSION
PONV is of multifactorial origin. The factors affecting PONV include patient-related factors (age, sex, and phase of the menstrual cycle), anesthesia related factors (use of volatile anesthetic agents, N2 O, and opioid), and surgery-related factors. Our study was aimed at comparing the efficacy of Ramosetron and Levosulpiride in preventing PONV in laparoscopic surgery . In our study, the factors that would have contributed to nausea and vomiting may be laparoscopic surgery (laparoscopic hernia repair, laparoscopic cholecystectomy, and laparoscopic gynecologic surgery), use of isoflurane, and use of fentanyl. Use of NG tube, use of nitrous oxide may or may not have contributed to nausea andvomiting.
Laparoscopic surgery was chosen because of high incidence of PONV associated with it. Naguib et al . demonstrated that the incidence of PONV after laparoscopic surgeries in their placebo group was remarkably high (72%).[13
We have conducted studies on 200 patients of ASA PS classes I and II with demographic data in terms of age, weight, which were similar in the two groups. There was no significant difference in Ramosetron and Levosulpiride (P < 0.05) in terms of age and weight.
Our study shows no statistically significant difference in the baseline values of hemodynamic variables between the two groups before, during or after giving study drug. Study drugs Ramosertron and Levosulpiride were given approximately half an hour after the induction of the anesthesia. In our study, the incidence of nausea and vomiting is 29% in Levosulpiride group over 24 h, with lesser incidence of PONV in Levosulpiride group than Ramosetron group with 29% and 39% incidence of PONV, respectively, but found to be statistically insignificant. Levosulpiride 25 mg i.v. and Ramosetron 0.3 mg i.v. is effective in control of PONV in patients undergoing elective laparoscopic surgery under general anesthesia. Similarly, in a study done by Kaul et al .[7 et al .[14 Levosulpiride compared to control group.
Lee et al .[15 Ramosetron 0.3 mg i.v. is equally effective in the prevention of PONV as Palonostron 0.075 mg i.v. and Granisetron group 3 mg i.v. Park et al .[16 Ramosetron group during 06 h (6% vs. 26%, P = 0.012) and 048 h (14% vs. 34%, P = 0.034).
Ryu et al .[17 Ramosetron 0.3 mg and Ondansetron 8 mg are more effective than Ondansetron 4 mg for the prevention of PONV (2 h).
CONCLUSION
This study concludes that the prophylactic i.v. administration of Levosulpiride and Ramosetron are equally effective in controlling postoperative nausea and vomiting in patients undergoing laparoscopic surgery under general anesthesia.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Lichtor JL, Glass PS. We’re tired of waiting Anesth Analg. 2008;107:353–5
2. Fisher DM. The “big little problem” of
postoperative nausea and vomiting : Do we know the answer yet? Anesthesiology. 1997;87:1271–3
3. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, et al Department of Anesthesiology DUMC Consensus guidelines for managing
postoperative nausea and vomiting Anesth Analg. 2003;97:62–71
4. Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients Anesth Analg. 1999;89:652–8
5. Apfel CCMiller RD.
Postoperative nausea and vomiting Miller's Anesthesia. 20107th ed Philadelphia Churchill Livingstone:2729–55
6. Song CW, Chun HJ, Kim CD, Ryu HS, Choe JG, Hyun JH. Effects of
levosulpiride in patients with functional dyspepsia accompanied by delayed gastric emptying Korean J Intern Med. 1998;13:15–21
7. Kaul A, Kumar V, Sodhi BS, Sharma K. Prevention of post-operative nausea and vomiting following laparoscopic cholecystectomy Int J Sci Stud. 2017;5:200–6
8. Corli O, Cozzolino A, Battaiotto L. Effectiveness of
levosulpiride versus metoclopramide for nausea and vomiting in advanced cancer patients: A double-blind, randomized, crossover study J Pain Symptom Manage. 1995;10:521–6
9. Zanoboni A, Forgione A, Zanussi C. Antiemetic efficacy and safety of L-sulpiride in patients with digestive and other disorders Curr Ther Res. 1987;41:903–14
10. Kim SI, Kim SC, Baek YH, Ok SY, Kim SH. Comparison of
ramosetron with ondansetron for prevention of
postoperative nausea and vomiting in patients undergoing gynaecological surgery Br J Anaesth. 2009;103:549–53
11. Fujii Y, Saitoh Y, Tanaka H, Toyooka H.
Ramosetron for preventing
postoperative nausea and vomiting in women undergoing gynecological surgery Anesth Analg. 2000;90:472–5
12. Park HE, Kim MK, Kang WK. Efficacy and safety of
Ramosetron injection for nausea and vomiting in colorectal-cancer patients undergoing a laparoscopic colectomy: A randomized, double-blind, comparative study Ann Coloproctol. 2018;34:36–41
13. Naguib M, el Bakry AK, Khoshim MH, Channa AB, el Gammal M, el Gammal K, et al Prophylactic antiemetic therapy with ondansetron, tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: A randomized, double-blind comparison with placebo Can J Anaesth. 1996;43:226–31
14. Sharma R, Goyal P, Wadhwa M, Gupta M, Mandial V, Jaswal KS. Efficacy of levosulpride in minimizing post-operative nausea and vomiting after laparoscopic cholecystectomy Int J Contemp Med Res. 2019;6:35–9
15. Lee WS, Lee KB, Lim S, Chang YG. Comparison of palonosetron, granisetron, and
ramosetron for the prevention of
postoperative nausea and vomiting after laparoscopic gynecologic surgery: A prospective randomized trial BMC Anesthesiol. 2015;15:121
16. Park SK, Cho EJ, Kang SH, Lee YJ, Kim DA. A randomized, double-blindstudy to evaluate the efficacy of
ramosetron and palonosetron for prevention ofpostoperative nausea and vomiting after gynecological
laparoscopic surgery Korean J Anesthesiol. 2013;64:133–7
17. Ryu J, So YM, Hwang J, Do SH.
Ramosetron versus ondansetron for the prevention of
postoperative nausea and vomiting after laparoscopic cholecystectomy Surg Endosc. 2010;24:812–7
